P1010: PATIENTS WITH MYELOPROLIFERATIVE NEOPLASMS HAVE INCREASED NUMBERS OF MYELOID-DERIVED SUPPRESSOR CELLS, AND DECITABINE MAY HAVE A SIGNIFICANT THERAPEUTIC EFFECT IN MPN PATIENTS WITH HIGH MDSCS
Authors: Qiutian Feng, Shiwei Hu, Danhong Xiang, Xinlu Zhang, Lan Zhang, Shengjie Wang, Xiaoqiong Zhu, Jian Huang
Journal: HemaSphere (2023)

Topic: 15. Myeloproliferative neoplasms - Biology & Translational Research Background: Classic Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) are a group of diverse hematopoietic stem cell disorders. The pathogenesis of MPNs remains unknown, and currently available treatments have limited efficacy. Recent research has shown that the immunosuppressive tumor microenvironment plays a crucial role in the development of MPNs,and myeloid-derived suppressor cells (MDSCs) serve as key inhibitory cells that contribute to the formation of a suppressive immune microenvironment. Aims: This retrospective study aimed to compare the quantity of MDSCs in bone marrow samples obtained from patients with various types of MPNs and healthy control individuals. The study investigated the inhibitory effect of different doses of the demethylating agent decitabine (HMA) on MDSCs in bone marrow samples from MPN patients. Methods: In this retrospective study, flow cytometry was utilized to identify the Lin-HLA-DR-CD33+ labeled MDSCs in bone marrow specimens collected from a cohort of 100 patients with diverse subtypes of myeloproliferative neoplasms, including polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF), post-ET myelofibrosis (post-ET MF), and post-PV myelofibrosis (post-PV MF), as well as 20 healthy controls. For MPN patients with high bone marrow MDSCs, decitabine was administered at varying concentrations ranging from 0μmol/L to 2.0μmol/L, and the remaining MDSCs were quantified via flow cytometry at 24h, 48h, and 72h after drug exposure. Results: The results of flow cytometry (Figure a) showed that the number of MDSCs in the bone marrow of MPN patients of different types was 19.8±5.72%, significantly higher than that in the normal control group (1.72±0.88%, p<0.0001). Specifically, the PV group had 17.49±5.75%, the ET group had 15.47±5.29%, the PMF group had 26.86±6.17%, the post-ET MF group had 18.10±4.77%, and the post-PV MF group had 12.58±3.65%, with the PMF group having the highest count (p<0.001) (Figure b). Next, bone marrow samples from three MPN patients with different initial MDSC counts (20.15%, 20.80%, and 9.05%) were treated with decitabine at concentrations of 0 μmol/L, 0.25 μmol/L, 0.5 μmol/L, 1 μmol/L, and 2 μmol/L (Figure c). As the concentration and duration of decitabine increased, the number of MDSCs gradually decreased (Figure d). Summary/Conclusion: The experimental results showed that there were differences and specificities in the number of MDSCs between MPN patients and normal individuals, and different doses of the demethylating agent decitabine may have considerable clinical efficacy in treating different types of MPN patients with increased MDSCs. This research was funded by the Key R&D Program of Zhejiang, No. 2022C03137; Public Technology Application Research Program of Zhejiang, China, No. LGF21H080003; Zhejiang Medical Association Clinical Medical Research special fund project, No. 2022ZYC-D09; the Key Project of Jinhua Science and Technology Plan, China, No. 2020-3-011.*Correspondence to:Prof Jian Huang.Keywords: Myeloproliferative disorder, decitabine